The proposed research for the second year of the grant will be a continuation of the work started in the first year. The methodology to be employed will be essentially the same: antral tissue culture methods will be used for studying the relationships between somatostatin and GRP and their effects on gastric release. The methods will also be utilized to examine other members of the secretin family (GIP and VIP) and their effects on the relationship between somatostatin and gastrin. The in situ isolated perfused rat stomach will also be utilized to investigate interactions among the various gastrointestinal regulatory peptides. This will be primarily used for peptides which appear to exert their effect through hormonal means, such as GIP and secretin. In addition, because of our development of an isolated vascularly perfused rat stomach model capable of secreting acid, we will be able to directly study the effects of these peptides on the release of gastric acid. Finally, if time permits, we will study the effects of these peptides on gastric acid secretion in in vivo preparations; dogs will be prepared with gastric fistulas and gastric acid secretion will be studied in response to various physiologic stimuli. The proposed research should help to clarify the complex relationships between candidate enterogastrones - GIP, VIP and secretin - and somatostatin. It will also enable us to investigate the relationship between these peptides and gastrin - releasing peptide. The research should help up define the role of these peptides in the regulation of gastrin release, and whether this regulation is physiologically mediated through effects on somatostatin.